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Doc Nr: UIC-MOP-APP-023
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Département d’oncologie
Centre de Thérapies Expérimentales
Unité d’Investigation Clinique (UIC)
Appendix
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Indication
Cancer gastrique ou jonction gastro-œsophagienne
Title
A INtegratioN of trastuzumab, with or without pertuzumab, into
periOperatiVe chemotherApy of HER-2 posiTIve stOmachc aNcer :
the INNOVATION-TRIAL
Protocol ID
EORTC-1203-GITCG
Phase
II
Sponsor
EORTC
Principal
Investigator
Dr. A. Wagner
Primary Objective
The objective of the trial is to increase the major pathological response rate (<
10% vital tumor cells) to neoadjuvant treatment by integrating both
trastuzumab and pertuzumab into perioperative chemotherapy for HER-2
positive, resectable gastric cancer.
Inclusion/exclusio
n criteria
Patient selection criteria - Registration
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Assessment of the HER-2 status by IHC.
All patients (HER-2 positive and negative) should be registered in the
trial as soon as possible after written informed consent for screening
according to ICH/GCP, and national/local regulations.
Histologically proven, gastric or GE-junction adenocarcinoma (Siewert
I-III)
Absence of distant metastases on CT scan of thorax and abdomen
Patient medically fit for gastrectomy/oesophagectomy as decided by
the investigator
Age > 18 years
WHO performance status 0 – 1
HER2 status
Availability of the paraffin block or sufficient (ideally 20x 3-5 µm
slides, but exceptionally minimum 15 slides is acceptable) unstained
paraffin sections from the diagnostic endoscopic biopsies for
centralized HER-2 assessment/confirmation.
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Patient selection criteria - Randomization
♦ HER-2 overexpression, as determined by central testing using
immunohistochemistry (IHC 3+) or the combination of IHC 2+ and HER-2
FISH positive.
♦ Amenable to gastrectomy/oesophagectomy with curative intent as confirmed
by a multidisciplinary team discussion
♦ UICC tumor stage Ib to III, as defined by CT (CT should be assessed within
35 days prior to start of treatment). Endosonography (EUS) is recommended,
but not mandatory. EUS should especially be considered to distinguish T1 and
T2 tumors and to evaluate local resectability. (In case of conflicting results of
CT and endoscopic ultrasound, the final decision on which finding the staging
is based should be taken by the multidisciplinary team, please refer to chapter
6.3.1 for reporting).
♦ No prior chemo- or antibody therapy
♦ No history of significant cardiac disease defined as:
♦ Symptomatic CHF (NYHA classes II-IV)
♦ High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a heart rate >
100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or
higher-grade AV-block (second degree AV-block Type 2 [Mobitz 2] or third
degree AV-block)
♦ History of myocardial infarction within 6 months prior to randomization
 Clinically significant valvular heart disease
 Angina pectoris requiring anti-anginal treatment
♦ No current uncontrolled hypertension (persistent systolic > 180 mmHg
and/or diastolic > 100 mmHg)
♦ The cardiac ejection fraction (LVEF), as determined by echocardiography,
MUGA or cardiac MRI should be at least 55% (assessed within 14 days prior
to randomization).
♦ Adequate organ function (assessed within 7 days prior to randomization):
♦ White blood cell count (WBC) > 3 x 109/L
♦ Absolute neutrophil count (ANC) > 1.5 x 109/L
♦ Platelets ≥ 100 x 109/L
♦ Hemoglobin ≥ 9 g/dL
♦ Estimated glomerular filtration rate (eGFR) according to MDRD
should be > 60 ml/min
♦ Total bilirubin within normal limits (if the patient has documented
Gilbert’s disease ≤ 1.5 × ULN or direct bilirubin ≤ ULN)
♦ Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5
× ULN
♦ No known hypersensitivity to the components of trastuzumab, pertuzumab,
cisplatin, 5-FU or capecitabine
♦ No known dihydropyrimidine dehydrogenase (DPD) deficiency
♦ No ongoing or concomitant use of the antiviral drug sorivudine or its
chemically related analogs, such as brivudine
♦ No chronic treatment with high-dose intravenous corticosteroids
♦ Investigator and patient have to agree to replace any oral anticoagulations by
subcutaneous administration of low-molecular weight heparin (LMWH) in
equivalent doses before treatment start, or if on oral anticoagulations and
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unwilling to switch to LMWH, patients have to be treated with mandatory 5FU i.v. instead of capecitabine.
♦ No previous malignancy within the last 5 years, with the exception of
adequately treated cervical carcinoma in situ, localized non-melanoma skin
cancer, or other curatively treated cancer without impact on the patient’s
overall prognosis according to the judgment of the investigator.
♦ Absence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule; those conditions should be discussed with the patient
before registration in the trial
♦ For women who are not postmenopausal (> 12 months of non-therapy
induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus):
agreement to remain abstinent or use single or combined contraceptive
methods that result in a failure rate of < 1% per year during the treatment
period and for at least 7 months after the last treatment dose
♦ For men: agreement to remain abstinent or use a condom plus an additional
contraceptive method that together result in a failure rate of < 1% per year
during the treatment period and for at least 7 months after the last dose of study
treatment. Abstinence is only acceptable if it is in line with the preferred and
usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable
methods for contraception.
♦ For all female patients who are not confirmed postmenopausal (> 12 months
of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries
and/or uterus) a negative serum pregnancy test (β-human chorionic
gonadotropin [β-hCG]) result should be available before randomization and
within 7 days from treatment start should be performed. Female patients should
not be breast feeding.
♦ Before patient randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.
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